Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

OBJECTIVE To observe the clinical efficacy of Xuefu Zhuyu Decoction(XFZY)in the prevention and treatment of radiation-induced lung fibrosis(RILF)in esophageal cancer patients with blood stasis type underwent concurrent chemoradiotherapy(CRT).METHODS A total of 130 esophageal cancer patients with blood stasis type who treated with concurrent CRT were randomly divided into an experimental group and a control group,with 65 cases in each group.No patients dropped out during the study period.Patients in both groups received CRT and standardized symptomatic treatment was given according to the condition if radiation-induced lung injury occurred during treatment.On the basis of the treatment of the control group,the patients in the experimental group received XFZY from the beginning day until 30 days after the completion of CRT.The TCM syndrome score of the two groups were compared before and after treatment.The incidence of acute radiation pneumonia(RP)and chronic RILF and changes in pulmo-nary function indicators[forced expiratory volume in the first second as a percentage of predicted value(FEV1%pred),forced vital ca-pacity(FVC),FVC as a percentage of predicted value(FVC%pred),FEV1/FVC ratio,and carbon monoxide diffusing capacity as a per-centage of predicted value(DLCO%pred)]and serum cytokine levels[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),and transforming growth factor β1(TGF-β1)]were compared at 6 months and 12 months after the completion of CRT.The occurrence of adverse reaction during treatment was recorded.RESULTS The total score of TCM syndrome of the two groups was significantly improved and the experimental group was better than that of the control group(P<0.01)after treatment.The efficacy of TCM syndrome was better in the experimental group than that of the control group(P<0.01).There was no statistically significant difference in the incidence rate of acute RP between the two groups(P>0.05)at 6 months after the completion of CRT.The levels of lung function indicators FEV1%pred,FVC%pred,and DLCO%pred in the experimental group were higher than those in the control group(P<0.05),and the levels of various cytokines in the experimental group were lower than those in the control group(P<0.05).The incidence rate of chronic RILF in the experimental group was significantly lower than that of the control group(P<0.05)at 12 months after the completion of CRT.The DLCO%pred level in the experimental group was higher than that in the control group(P<0.01),and the levels of cytokines HIF-1α,VEGF,and TGF-β1 were lower than those in the control group(P<0.05,P<0.01).There was no serious adverse event observed in either group of patients during the treat-ment.CONCLUSION XFZY can effectively prevent and treat RILF in esophageal cancer patients with blood stasis type underwent CRT,reducing the loss to lung function caused by radiotherapy,and its mechanism may be related to downregulating the levels of cyto-kines of HIF-1α,VEGF,and TGF-β1.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

Accurate characterization of the chemical composition of complex traditional Chinese medicine(TCM)is an essential foundation for the modern scientific interpretation of TCM principles.Mass spectrometry is the most dominant technique in current research on the material basis of TCM,offering the highest sensitivity and the richest information provision.Establishing mass spectrometry databases represents the most effective approach to facilitating the structural analysis of TCM chemical components.This paper systematically searches and reviews literature published from January 2005 to January 2025 through online databases such as China National Knowledge Infrastructure,PubMed,and Web of Science,using"mass spectrometry database"and"traditional Chinese medicine"as keywords.It reviews the current status of seven TCM chemical component mass spectrometry databases and seven natural product mass spectrometry databases.The key advancements of these mass spectrometry databases for natural products are summarized,detailing their characteristics,search methodologies,included information,and data sources.Additionally,challenges related to data quality,standardization,timely updates,database interaction,retrieval functionality,and data sharing and security are discussed in depth.Furthermore,the paper explores prospective development directions for TCM mass spectrometry databases,emphasizing the importance of open data sharing,technological innovation,and data security.Through this analysis,the paper aims to offer theoretical guidance and practical recommendations for the precise identification of TCM components,as well as for the construction and application of these databases.

OBJECTIVE To observe the clinical efficacy of Xuefu Zhuyu Decoction(XFZY)in the prevention and treatment of radiation-induced lung fibrosis(RILF)in esophageal cancer patients with blood stasis type underwent concurrent chemoradiotherapy(CRT).METHODS A total of 130 esophageal cancer patients with blood stasis type who treated with concurrent CRT were randomly divided into an experimental group and a control group,with 65 cases in each group.No patients dropped out during the study period.Patients in both groups received CRT and standardized symptomatic treatment was given according to the condition if radiation-induced lung injury occurred during treatment.On the basis of the treatment of the control group,the patients in the experimental group received XFZY from the beginning day until 30 days after the completion of CRT.The TCM syndrome score of the two groups were compared before and after treatment.The incidence of acute radiation pneumonia(RP)and chronic RILF and changes in pulmo-nary function indicators[forced expiratory volume in the first second as a percentage of predicted value(FEV1%pred),forced vital ca-pacity(FVC),FVC as a percentage of predicted value(FVC%pred),FEV1/FVC ratio,and carbon monoxide diffusing capacity as a per-centage of predicted value(DLCO%pred)]and serum cytokine levels[interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),and transforming growth factor β1(TGF-β1)]were compared at 6 months and 12 months after the completion of CRT.The occurrence of adverse reaction during treatment was recorded.RESULTS The total score of TCM syndrome of the two groups was significantly improved and the experimental group was better than that of the control group(P<0.01)after treatment.The efficacy of TCM syndrome was better in the experimental group than that of the control group(P<0.01).There was no statistically significant difference in the incidence rate of acute RP between the two groups(P>0.05)at 6 months after the completion of CRT.The levels of lung function indicators FEV1%pred,FVC%pred,and DLCO%pred in the experimental group were higher than those in the control group(P<0.05),and the levels of various cytokines in the experimental group were lower than those in the control group(P<0.05).The incidence rate of chronic RILF in the experimental group was significantly lower than that of the control group(P<0.05)at 12 months after the completion of CRT.The DLCO%pred level in the experimental group was higher than that in the control group(P<0.01),and the levels of cytokines HIF-1α,VEGF,and TGF-β1 were lower than those in the control group(P<0.05,P<0.01).There was no serious adverse event observed in either group of patients during the treat-ment.CONCLUSION XFZY can effectively prevent and treat RILF in esophageal cancer patients with blood stasis type underwent CRT,reducing the loss to lung function caused by radiotherapy,and its mechanism may be related to downregulating the levels of cyto-kines of HIF-1α,VEGF,and TGF-β1.

Accurate characterization of the chemical composition of complex traditional Chinese medicine (TCM) is an essential foundation for the modern scientific interpretation of TCM principles. Mass spectrometry is the most dominant technique in current research on the material basis of TCM, offering the highest sensitivity and the richest information provision. Establishing mass spectrometry databases represents the most effective approach to facilitating the structural analysis of TCM chemical components. This paper systematically searches and reviews literature published from January 2005 to January 2025 through online databases such as China National Knowledge Infrastructure, PubMed, and Web of Science, using “mass spectrometry database” and “traditional Chinese medicine” as keywords. It reviews the current status of seven TCM chemical component mass spectrometry databases and seven natural product mass spectrometry databases. The key advancements of these mass spectrometry databases for natural products are summarized, detailing their characteristics, search methodologies, included information, and data sources. Additionally, challenges related to data quality, standardization, timely updates, database interaction, retrieval functionality, and data sharing and security are discussed in depth. Furthermore, the paper explores prospective development directions for TCM mass spectrometry databases, emphasizing the importance of open data sharing, technological innovation, and data security. Through this analysis, the paper aims to offer theoretical guidance and practical recommendations for the precise identification of TCM components, as well as for the construction and application of these databases.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint